DESCRIPTION: The current proposal will focus on the mechanisms of hematopoietic reconstitution following drug treatment, and utilize combination anti-retroviral therapy as an adjunct to assess the efficacy of various stem cell genetic therapeutic approaches to combat HIV-induced pathology. The specific aims include: (1) optimize and further define the loss and subsequent reconstitution of thymopoiesis seen following anti- retroviral treatment of HIV-infected Thy/Liv implants; (2) optimize and further define the mechanisms responsible for loss and subsequent reconstitution of non-lymphoid hematopoietic precursor activity in vivo; and (3) optimize in vivo efficacy of anti-viral gene therapeutic approaches in conjunction with pharmacologic anti-retroviral therapy.